The Bright Side of the “Depression-Risk Gene”

The reclamation of the “depression gene” proceeds apace: In a paper titled “Looking on the Bright Side of Serotonin Transporter Gene Variation,” two researchers who helped establish the “depression risk-gene” view of depression assert quite strongly that people with the gene variant in question — the s-allele of the serotonin transporter gene, HTTLPR — possess greater social sensitivity than do people without this variant, and hold certain cognitive advantages as well.

From the abstract:

Here, we review recent findings that humans and nonhuman primates carrying the s variant of the 5-HTTLPR outperform subjects carrying the long allele in an array of cognitive tasks and show increased social conformity. In addition, studies in 5-HTT knockout rodents are included that provide complementary insights in the beneficial effects of the 5-HTTLPR s-allele. We postulate that hypervigilance, mediated by hyperactivity in corticolimbic structures, may be the common denominator in the anxiety-related traits and (social) cognitive superiority of s-allele carriers and that environmental conditions determine whether a response will turn out to be negative (emotional) or positive (cognitive, in conformity with the social group). Taken together, these findings urge for a conceptual change in the current deficit-oriented connotation of the 5-HTTLPR variants. In fact, these factors may counterbalance or completely offset the negative consequences of the anxiety-related traits. This notion may not only explain the modest effect size of the 5-HTTLPR and inconsistent reports but may also lead to a more refined appreciation of allelic variation in 5-HTT function.

Faithful readers will recognize this as an idea I explored in my Atlantic feature last year, The Orchid Children: that certain ‘risk’ genes, among them the s-allele version of this serotonin transporter gene, create not just risk but a higher overall sensitivity that can create upsides. Many papers have provided data supporting this view. But other than reviews from psychologist Jay Belsky, who was one of the first to assert this notion, few scientists have articulated this idea as boldly and plainly as Judith Homberg and Karl-Peter Lesch do here. That Lesch first discovered the stress-reactivity created by the s-allele back in 1995 — opening the door to the ‘depression-risk-gene’ view of the s-allele — only heightens the impact of this call to see this ‘depression gene’ differently.

Call it the sensitivity gene, perhaps — or the orchid gene, as I called it in my article.

So what are some of the advantageous traits the s-allele can create? Its benefits (and downsides), Homberg and Lesch assert, rise from “hypervigilance.” By this they essentially mean an increased attention to social dynamics around them.

Physiologically, this shows in an especially reactive amygdala — a couple of deep-brain, almond-sized nuggets central to fear learning. The amygdala of S-allele carriers show more reaction to things like fearful faces, negative language, and other signs of threat. Yet as Homberg and Lesch point out, the amygdala plays a key role in a wide range of learning, both positive and negative, including (and perhaps especially) in social realms. The amygdala’s extra sensitivity in S-allele carriers may make them more attuned to social dynamics — improving their social cognition, say Homberg and Lesch, and some forms of non-social cognition as well.

These would-be depressives, for instance, do better in a particular “affective” type of go/no-go task, in which you have to stifle an intentional motor response based on the emotional valence of words; this presumably, because S-allele carriers better sense the emotional temperature of language. (Emotionally alert readers, take note — or had you already?)

S-allele carriers (S-S or S-L) have also done better than the more common L-allele carriers (L-L) in some gambling-based decision-making studies. In general they seem more sensitive to context. Rhesus macaques with an S-allele version of the same gene also show stronger cognition in a roughly similar array of tests. Finally, people with S alleles tend to have better episodic memory — memories of things that happened, rather than straight facts — than L-carriers do.

On the cognitive downside, S-allele people aren’t as good as L-allele carriers at remembering a noun if it occurs soon before another noun that is emotionally laden — as if the more charged noun made them forget its predecessor. They also don’t do as well as the infamous Iowa gambling task — possibly because that cognitive game has few emotional cues. There are quite a few cognitive tests in which the variant seems to have no effect.

Add it up, say Lomberg and Lesch, and you have a gene variant that, rather than just Creating depression risk, creates social sensitivity, increased attentiveness, and a “wide range of cognitive functions” that include improved decisions making and cognitive flexibility in many situations. This may provide an evolutionary advantage, since it seems to make people more sensitive to changes in environments and threats of different sorts. “They’re the ones,” as one researchers told me not long ago, “who, back in evolutionary time, would be the first to notice the strangers on the horizon.”
This happens to reach me as I fly to San Diego to attend the first meeting of the Society for Social Neuroscience and then the Society for Neuroscience meeting. I suspect this will be a major topic of discussion.

PS: Forgive the sparse linkage; the slow internet on this plane makes it rather difficult. I’ll try to make up for it later.

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